Cell-free DNA screening following first-trimester septated cystic hygroma leading to diagnosis of previously unknown familial Noonan syndrome

Current Perspectives of Prenatal Cell-free DNA Screening in Clinical Management of First-Trimester Septated Cystic Hygroma

“…First-trimester septated cystic hygroma (increased nuchal translucency and nonimmune hydrops) has been associated with Noonan syndrome (an autosomal dominant disorder characterized by short stature, congenital heart defects and distinctive facies). [98][99][100][101][102] This disorder is genetically heterogeneous with approximately 50% of patients demonstrating PTPN11 mutations. Studies of fetuses with cystic hygroma suggest a prevalence of 1-3% of Noonan syndrome.…”

“…This case was the first report of cfDNA screening after a finding of first-trimester septated cystic hygroma leading to the diagnosis of previously unestablished familial Noonan syndrome. 100 Pan et at al in 2020 described two cases of first-trimester septated cystic hygroma with normal karyotype and microarray workup in whom no additional structural anomalies were noted. 101 Subsequently the two infants manifested early developmental delays within two years of age.…”

“…2021.07.0566). 100

Figure 3 First-trimester septated fetal cystic hygroma in a 33 year-old, P2 at 11 and 5/7 weeks’ gestation. Non-invasive prenatal screening revealed increased risk of Trisomy 21.

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“…Sherer et al reported a case of first-trimester septated cystic hygroma in which cfDNA screening for serious single-gene disorders identifying a maternal pathogenic variant c.188A > G in PTPN11 ( Figure 2 ). 100 Due to the nature of cfDNA screening and the maternal contribution of cfDNA, this test was unable to confirm whether the fetus had inherited the maternal Noonan syndrome mutation (a 50% risk of direct inheritance). Confirmatory testing was performed for both the patient and cultured amniocytes, concluding a direct inheritance of Noonan syndrome.…”

“…This case was the first report of cfDNA screening after a finding of first-trimester septated cystic hygroma leading to the diagnosis of previously unestablished familial Noonan syndrome. 100 …”